P1088: COMPARISON OF BLEEDING-RELATED EVENTS IN PATIENTS WHO RECEIVED PIRTOBRUTINIB WITH AND WITHOUT ANTITHROMBOTIC AGENTS
Authors: Nicole Lamanna, Constantine Tam, Wojciech Jurczak, Arrin Kontos, Heiko Konig, Amy S. Ruppert, Donald E. Tsai
Journal: HemaSphere (2023)

Topic: 18. Indolent and mantle-cell non-Hodgkin lymphoma - Clinical Background: Though covalent Bruton tyrosine kinase inhibitors (BTKi) greatly improved outcomes in patients with B-cell malignancies, they are associated with an increased risk of bleeding events. Thus, prescribers are cautious about concomitant antithrombotic (anticoagulant/antiplatelet) use. Pirtobrutinib, a non-covalent (reversible) BTKi FDA approved for treatment of R/R MCL after 2 lines of therapy including a BTKi, demonstrated efficacy and tolerability across multiple B-cell malignancies. The incidence of bleeding events in patients treated with pirtobrutinib and concomitant antithrombotic therapy has not been specifically reported. Aims: To analyze bleeding events in patients from the BRUIN study who received pirtobrutinib with antithrombotic therapy. Methods: Patients with B-cell malignancies (317 CLL, 166 MCL, 290 other) who enrolled in the open-label, multicenter, Phase 1/2 BRUIN study (NCT03740529) were analyzed. Concomitant antithrombotic therapy (direct factor XA inhibitors, heparin anticoagulants, platelet aggregation inhibitors) at time of enrolment was permitted (excluding warfarin). Pirtobrutinib was administered once daily in 28-day cycles until disease progression or discontinuation due to toxicity. Common Terminology Criteria for Adverse Events V5.0 were used to determine grade and type of bleeding events. Descriptive analyses were performed. Results: As of 29 July 2022, 773 patients received at least one dose of pirtobrutinib monotherapy, including 216 patients with concomitant antithrombotic therapy. Among those with antithrombotic therapy, median age was 72 years (IQR: 65-77) and the proportion who were ≥75 years of age was 34%. Median time on pirtobrutinib treatment for patients with and without antithrombotic therapy was 10.6 (IQR: 4.0-19.9) and 9.3 months (IQR: 3.1-17.3), respectively. Any grade bleeding events were reported in 44.9% (97/216) of patients with antithrombotic therapy compared to 32.5% (181/557) of patients without antithrombotic therapy. A summary of bleeding events by type and severity in both groups is shown below (Table). Most bleeding events (>90%) in both groups were grade ≤2. The most common bleeding events (≥3%) in those with antithrombotic therapy were contusion (22.7%), hematuria (5.6%), epistaxis (5.1%), petechiae (3.7%), and hematoma (3.2%). Of the 6 (2.8%) patients on antithrombotic therapy who had a grade 3 bleeding event, 2 (0.9%) were deemed related to pirtobrutinib by investigators: an upper GI bleeding with anemia and a hemarthrosis from a knee injury (1 each). Grade ≥3 bleeding events occurred in 11 (2%) patients not taking antithrombotics. Any grade hemorrhage or hematoma occurred in 13/79 (16.5%) patients who received direct factor XA inhibitors, 10/39 (25.6%) patients who received heparins and 18/112 (16.1%) patients who received platelet aggregation inhibitors (some patients received >1 class). Among those with antithrombotic therapy, median time to onset of any grade bleeding event was 8.1 weeks (IQR: 2.6-24) and median duration of a bleeding event was 2.1 weeks (IQR: 0.6-4.3). Among those who received antithrombotic therapy, bleeding events required dose interruption of pirtobrutinib in 5 patients (2.3%), and no bleeding events led to dose reduction or permanent discontinuation of pirtobrutinib. Summary/Conclusion: Concomitant antithrombotic therapy with pirtobrutinib was associated with an increased rate of bleeding events relative to pirtobrutinib alone, though most events were grade ≤2. High-grade bleeding events were infrequent (<2%) among all patients. These data support the safety of pirtobrutinib administration in patients requiring antithrombotic therapies.Keywords: Clinical trial, Antithrombotic therapy, Bruton’s tyrosine kinase inhibitor (BTKi), Bleeding